L-cysteine Prevents Stomach Exposure to Carcinogenic Acetaldehyde

Per Hellström

Status and phase: Completed; Phase 2

Conditions: Gastritis, Atrophic

Treatments: Dietary Supplement: Slow-release L-cysteine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02524262

620070-SWE-2012

Details and patient eligibility

About

Atrophic gastritis with hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonizing the acid-free stomach oxidize ethanol into acetaldehyde, a group 1 carcinogen. The aim is to assess gastric production of acetaldehyde and its inert condensation product, non-toxic 4-methyltiazolidine-2-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo.

Patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 are studied. On separate days, patients will be randomly assigned to receive 200 mg slow-release L-cysteine or placebo, then have intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of acetaldehyde, ethanol, L-cysteine and MTCA are analysed for 4 hours.

Expected results show mitigated exposure of the gastric mucosa to acetaldehyde.

Full description

Gastric infection with Helicobacter pylori induces chronic active gastritis which over the years develop atrophic gastritis with a hypochlorhydric milieu which is a risk factor for gastric cancer. Microbes colonizing acid-free stomach oxidize ethanol into acetaldehyde, considered a group 1 carcinogen.

The aim of the study is to assess the gastric production of acetaldehyde and its inert condensation product, non-toxic 4-methyltiazolidine-2-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine. Identical placebo tablets will be used for comparison.

Patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 will be studied with case-control design. All subjects will be their own control. On separate days, patients are randomly assigned to receive 200 mg slow-release L-cysteine or placebo, then have intragastric instillation of 15% (0.3 g/kg) ethanol (corresponding to two glasses of wine). After intake, gastric sampling of fluid for a period of four hours is done and concentrations of acetaldehyde, ethanol, L-cysteine and MTCA are analysed.

L-cysteine is expected to decrease gastric acetaldehyde concentrations and increase the MTCA level. Gastric L-cysteine and MTCA concentrations are expected to be maintained over the study period. With placebo, acetaldehyde is expected to be elevated along with ethanol concentrations.

Based on these assumptions slow-release L-cysteine binds acetaldehyde to form inactive MTCA, which remains in gastric juice resulting in reduced local exposure of the gastric mucosa to carcinogenic acetaldehyde.

Enrollment: 8 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Helicobacter-associated chronic gastritis
• Hypochlorhydria
• Hypergastrinemia
• Hypopepsinogenemia

Exclusion criteria

• Active peptic ulcer disease
• Other inflammatory gastrointestinal disease
• Gastrointestinal bleeding
• Gastrointestinal surgery
• Neurological disease
• Alcohol abuse
• Mental disorder
• Not able to sign informed consent

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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8 participants in 2 patient groups, including a placebo group

Slow-release L-cysteine

Experimental group

Description:

Oral intake of slow-release L-cysteine 200 mg before challenge with ethanol.

Treatment:

Dietary Supplement: Slow-release L-cysteine

Placebo

Placebo Comparator group

Description:

Oral intake of identically-looking placebo capsules

Treatment:

Dietary Supplement: Slow-release L-cysteine